Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression
Cancer Epidemiology Biomarkers and Prevention
Background: Despite accumulating evidence for the preventive effect of vitamin D on colorectal carcinogenesis, its precise mechanisms remain unclear. We hypothesized that vitamin D was associated with a lower risk of colorectal cancer with high-level vitamin D receptor (VDR) expression, but not with risk of tumor with low-level VDR expression. Methods: Among 140,418 participants followed from 1986 through 2008 in the Nurses' Health Study and the Health Professionals' Follow-up Study, we identified 1,059 incident colorectal cancer cases with tumor molecular data. The predicted 25-hydroxyvitamin D [25(OH)D] score was developed using the known determinants of plasma 25(OH)D. We estimated the HR for cancer subtypes using the duplication method Cox proportional hazards model. Results: A higher predicted 25(OH)D score was associated with a lower risk of colorectal cancer irrespective of VDR expression level (P heterogeneity for subtypes = 0.75). Multivariate HRs (95% confidence intervals) comparing the highest with the lowest quintile of predicted 25(OH)D scores were 0.48 (0.30-0.78) for VDR-negative tumor and 0.56 (0.42-0.75) for VDR-positive tumor. Similarly, the significant inverse associations of the predicted 25(OH)D score with colorectal cancer risk did not significantly differ by KRAS, BRAF, or PIK3CA status (Pheterogeneity for subtypes ≥ 0.22). Conclusions: A higher predicted vitamin D score was significantly associated with a lower colorectal cancer risk, regardless of VDR status and other molecular features examined. Impact: The preventive effect of vitamin D on colorectal carcinogenesis may not totally depend on tumor factors. Host factors (such as local and systemic immunity) may need to be considered. © 2014 American Association for Cancer Research.
Jung, S., Qian, Z., Yamauchi, M., Bertrand, K., Fitzgerald, K., Inamura, K., Kim, S., Mima, K., Sukawa, Y., Zhang, X., Wang, M., Smith-Warner, S., Wu, K., Fuchs, C., Chan, A., Giovannucci, E., Ng, K., Cho, E., Ogino, S., & Nishihara, R. (2014). Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression. Cancer Epidemiology Biomarkers and Prevention, 23 (8). http://dx.doi.org/10.1158/1055-9965.EPI-14-0229